title: Effect of suppressive oligodeoxynucleotides on the development of inflammation-induced papillomas.
abstract: Inflammation contributes to the development of papillomas and squamous cell carcinomas in the well-established 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-l3-acetate (TPA) model of skin carcinogenesis. Synthetic oligonucleotides (ODN) containing repetitive TTAGGG motifs have been shown to block deleterious inflammatory reactions in murine models of autoimmunity, pneumonitis, and shock. This article examines whether treatment with suppressive (Sup) ODN can interfere with DMBA/TPA-induced inflammation, thereby reducing papilloma formation. Results indicate that Sup ODN block TPA-dependent skin hyperplasia, edema, and leukocytic infiltration. Sup ODN also inhibit the upregulation of genes encoding pro-oncogenic chemokines and other markers of inflammation including CXCL2, CCL2, COX-2, and ODC (ornithine decarboxylase). Of greatest import, Sup ODN reduce papilloma formation in a dose- and sequence-dependent manner. These findings suggest that Sup ODN may provide a novel means of preventing inflammation and associated oncogenesis.
authors.affiliation: Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Ikeuchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kinjo
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Klinman
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism; D010212:Papilloma / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
chemical_list: D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D015127:9,10-Dimethyl-1,2-benzanthracene; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate